DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Formula 2, wherein X7: Thr, X10: Tyr, X12: Lys, X15: Asp, X16: Glu, X17: Arg, X20:Lys, X21: Glu, and X24: Gln; and amino acid sequence of SEQ ID NO: 37 in the reply filed on 11/3/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Status of Application, Amendments, And/Or Claims
Claims 32-56 are pending and under consideration to the extent they read on the elected species.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 11/22/2022 and 11/7/2024 have been considered.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 32-38 and 41-56 are rejected under 35 U.S.C. 103 as being unpatentable over AU 2013342321 (WO 2014/073842) in view of Kim et al.1 (US Pub. No.2017/013802) and Kim et al.2 (US Pat. No. 10,696,725)
The instantly claimed invention is broadly drawn to a liquid formulation of a long-acting conjugate, wherein the liquid formulation comprises: 18 nmol/mL to 936 nmol/mL of a long-acting conjugate of Formula 1 below; a buffering agent in an amount for maintaining a pH of the liquid formulation in a range of 4.8 to 6.5; and 1.0%(w/v) to 20% (w/v) of a sugar alcohol, a saccharide, or a combination thereof: [Formula 1] X-La-F in Formula 1 above, L is a linker; a is 0 or a natural number, with the proviso that when a is 2 or more, each L is independent of each other; F is an immunoglobulin Fc fragment; - represents a covalent bond; and X is a glucagon derivative peptide of amino acid sequence of SEQ ID NO: 37(claims 32-35), wherein the X is amidated at the C-terminus; and/or wherein the X is linked via a sulfur atom of cysteine (claim 36), wherein the immunoglobulin Fc fragment is derived from IgG4.
AU 2013342321 teaches a liquid formulation of protein conjugate and an Fc, wherein the protein can be oxyntomodulin or glucagon for treating obesity (pg. 2, paragraph 6, pg. 5, paragraph [21])). They teach that the liquid formulation is albumin-free stabilizer, wherein the stabilizer contains a buffer, sugar alcohol, and non-ionic surfactant. They teach that the stabilizer may further include one or more components from isotonic agent, sugars, polyhydric alcohols and amino acids. They teach that the conjugate is in an effective amount (see pg. 6, para [26]) and it is noted that the effective amount of a peptide including GLP-1 variant, derivative or oxyntomodulin would be within the reach of one ordinary skill in the art. They teach using oxyntomodulin in a concentration of 10 mg/mL or 40 mg/mL, which would be within the range of 90 mmol/ml to 562 mmol/ml, unless evidence to contrary (see Tables 2, 26). They teach that sugar alcohol includes sorbitol, mannitol, glycerol in concentration of 2-15% (w/w) (page 6, para [24]). They teach that the buffer may include citrate, acetate, histidine or phosphate buffers to achieve a pH in the range of 4.5-7.0, more specifically 5-6 pH (pg.6, para [24], pg. 7, [29]). They teach that the isotonic agent may be NaCl, and non-ionic surfactant including polysorbate or poloxamer in a concentration of 0.0001-0.1% (w/v) (pg. 6 para [24]). They teach that the polysorbate is polysorbate 20 (pg. 6, para [26]). They teach that the amino acid may be methionine (page 6, para [24]). AU 2013342321 does not teach a conjugate of glucagon analog having amino acid sequence of SEQ ID NO: 37 conjugated with an Fc via a non-peptide linker.
Kim et al.1 teach a composition for prevention and treatment of diabetes including a long-acting insulinotropic peptide conjugate (see paragraph [0002]). They teach that the insulinotropic peptide includes GLP-1 and GLP-1 receptor agonists [0005]. They teach that a long-acting insulinotropic peptide is conjugated with an Fc via a non-peptidyl polymer as a linker by a covalent bond [0013]. They teach that the conjugate is represented by Formula: X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071]. They teach that the antibody fragment may be an Fc and can comprise a dimer or multimer formed from two or more fragments selected from the group consisting of IgG Fc, IgA Fc, IgM Fc, IgD Fc and IgE Fc fragments[0085]. They teach that the PEG is in a range of 1 to 20 kDa or 1 to 100kDa [0090].They teach that the pharmaceutical can be prepared in the form as per need in different form and determined by several related factors including the types of diseases to be treated, administration routes, patients age, gender, weight and severity of the illness [0108]. They teach that the pharmaceutical composition comprises pharmaceutically acceptable carriers such as a binder, a solubilizer, an excipient, a buffering agent, an isotonic agent [0109]. They teach that a formulation is in a form for solution (liquid), suspension or other forms and they comprise a carrier such as mannitol, sucrose, sorbitol, lactose [0110]. They teach that the pharmaceutical composition comprises stabilizer [0109]. They do not teach that the insulinotropic peptide X comprises amino acid sequence of SEQ ID NO: 37 and that the pH of the comprising is in a range of 4.8 to 6.5, and that the sugar alcohol in in a range of 1.0% to 20% (w/v).
Kim et al.2 teach that a pharmaceutical composition comprising glucagon derivative, a long-acting conjugate of glucagon and a use thereof for treating metabolic syndrome. They teach a glucagon derivative of amino acid sequence of SEQ ID NO: 37 which is 100% similar to the instantly claimed amino acid sequence of SEQ ID NO: 37(see sequence alignment below). They teach that the glucagon derivative is conjugated with an Fc by a non-peptidyl linker, PEG (see col. 7-8). They teach that the Fc may be a dimer (col. 21, lines 51+). They teach that the Fc is in the form of aglycosylated (or deglycosylated) (col. 7, line 46+). They teach that since glucagon has a pH of about 7, it is insoluble in a physiological pH (4-8) and it is in solution at pH 3 or below (col. 12). They teach that the glucagon derivatives have improved solubility at or near neutral pH (col. 13, lines 11+). They teach that the glucagon derivative has pH value of from 4 to 6.5 and therefore, the derivative can be lower than or near neutral pH as compared to native glucagon (col. 12, lines63+ to col. 13). They teach that X is linked to PEG via lysine or thiol group of cysteine of glucagon (col. 20, lines 19+ and col. 21, Lines 1+).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a glucagon derivative of SEQ ID NO: 37 as taught by Kim et al.2 in combination with Kim et al.1 in a liquid formulation as taught by AU 2013342321. Additionally, one would have been motivated to do so because Kim et al1. and Kim et al.2 teach glucagon derivatives conjugated with an Fc by a non-peptidyl linker. Further, one would have a reasonable expectation of success in using a glucagon derivative having amino acid sequence of SEQ ID NO: 37 as taught by Kim et al.2 to conjugate with an Fc by a non-peptide linker PEG.
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Claim(s) 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over AU 2013342321 (WO 2014/073842) in view of Kim et al.1 (US Pub. No.2017/013802) and Kim et al.2 (US Pat. No. 10,696,725) as applied to claims 32-38 and 41-56 above, and further in view of Kim et al.3 ( US Pub. No. 2018/0326013, also published as US 11,389,508).
The instantly claimed invention is further drawn to a liquid formulation of a long-acting conjugate, wherein the liquid formulation comprises: 18 nmol/mL to 936 nmol/mL of a long-acting conjugate of Formula 1 below; a buffering agent in an amount for maintaining a pH of the liquid formulation in a range of 4.8 to 6.5; and 1.0%(w/v) to 20% (w/v) of a sugar alcohol, a saccharide, or a combination thereof: [Formula 1] X-La-F in Formula 1 above, L is a linker; a is 0 or a natural number, with the proviso that when a is 2 or more, each L is independent of each other; F is an immunoglobulin Fc fragment; - represents a covalent bond; and X is a glucagon derivative peptide of amino acid sequence of SEQ ID NO: 37(claims 32-35), wherein the X is amidated at the C-terminus; and/or wherein the X is linked via a sulfur atom of cysteine (claim 36), wherein the immunoglobulin Fc fragment is derived from IgG4, wherein the F is a homodimer of monomers of the amino acid sequence of SEQ ID NO: 51 and wherein F is linked through a nitrogen atom of proline at the N-terminus thereof.
The teachings of AU 2013342321 (WO 2014/073842), Kim et al.1 and Kim et al.2 are set forth above. Neither AU 2013342321, Kim et al.1 nor Kim et al.2 teaches that an immunoglobulin Fc has amino acid sequence of SEQ ID NO: 51, wherein F is linked through a nitrogen atom of proline at the N-terminus.
Kim et al.3 teach a modified Fc that has proline at the N-terminus and it provides a superior product and the Fc can be to prepare for long-acting formulation [0009]. They teach many conjugates including exendin-4 to attach a non-peptide linker at a nitrogen atom of proline as the Fc fragment (see paragraph [0242]) and that it results in more than 90% selectivity of the product [0091]. They teach that the amino acid sequence of the Fc has amino acid sequence of SEQ ID NO: 1 which is identical to the instantly claimed Fc fragment of SEQ ID NO: 51 (see below).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use an immunoglobulin Fc having amino acid sequence of SEQ ID NO: 51 to attach at the N-terminus of proline with PEG as taught by Kim et al.3 to prepare a liquid comprising a protein conjugate having the formula X-La-F as taught by AU 2013342321 in combination with Kim et al.1 and Kim et al.2 Additionally, one would have been motivated to do so because Kim et al3. teach that the attachment of a peptide via a non-peptidyl linker results in more than 90% specific product [0091]. Further, one would have a reasonable expectation of success in using an immunoglobulin Fc comprising proline at the N-terminus of SEQ ID NO: 51 to conjugate with the instant glucagon derivative because Kim et al3 teaches that such conjugation results in a specific product with high specificity (more than 90% specific) product. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
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Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 32-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10,696,725 in view of AU 2013342321 (WO 2014/073842) and Kim et al.1 (US Pub. No.2017/013802). Claims 1-12 of US Patent No. 10,696,725 teach a glucagon conjugate comprising a glucagon derivative of amino acid sequence of SEQ ID NO: 37 conjugated with an Fc via a non-peptidyl linker. Claims 1-12 of US Patent No. 10,696,725 do not teach a liquid composition comprising a buffering agent in amount of maintaining a pH of the liquid formulation in a range of 4.8 to 6.5 and 1% (w/v) to 20% (w/v) of sugar alcohol, a saccharide or a combination thereof.
AU 2013342321 teaches a liquid formulation of protein conjugate and an Fc, wherein the protein can be oxyntomodulin or glucagon for treating obesity (pg. 2, paragraph 6, pg. 5, paragraph [21])). They teach that the liquid formulation is albumin-free stabilizer, wherein the stabilizer contains a buffer, sugar alcohol, and non-ionic surfactant. They teach that the stabilizer may further include one or more components from isotonic agent, sugars, polyhydric alcohols and amino acids. They teach that the conjugate is in an effective amount (see pg. 6, para [26]) and it is noted that the effective amount of a peptide including GLP-1 variant, derivative or oxyntomodulin would be within the reach of one ordinary skill in the art. They teach using oxyntomodulin in a concentration of 10 mg/mL or 40 mg/mL, which would be within the range of 90 mmol/ml to 562 mmol/ml, unless evidence to contrary (see Tables 2, 26). They teach that sugar alcohol includes sorbitol, mannitol, glycerol in concentration of 2-15% (w/w) (page 6, para [24]). They teach that the buffer may include citrate, acetate, histidine or phosphate buffers to achieve a pH in the range of 4.5-7.0, more specifically 5-6 pH (pg.6, para [24], pg. 7, [29]). They teach that the isotonic agent may be NaCl, and non-ionic surfactant including polysorbate or poloxamer in a concentration of 0.0001-0.1% (w/v) (pg. 6 para [24]). They teach that the polysorbate is polysorbate 20 (pg. 6, para [26]). They teach that the amino acid may be methionine (page 6, para [24]).
Kim et al.1 teach a composition for prevention and treatment of diabetes including a long-acting insulinotropic peptide conjugate (see paragraph [0002]). They teach that the insulinotropic peptide includes GLP-1 and GLP-1 receptor agonists [0005]. They teach that a long-acting insulinotropic peptide is conjugated with an Fc via a non-peptidyl polymer as a linker by a covalent bond [0013]. They teach that the conjugate is represented by Formula: X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071]. They teach that the antibody fragment may be an Fc and can comprise a dimer or multimer formed from two or more fragments selected from the group consisting of IgG Fc, IgA Fc, IgM Fc, IgD Fc and IgE Fc fragments[0085]. They teach that the PEG is in a range of 1 to 20 kDa or 1 to 100kDa [0090].They teach that the pharmaceutical can be prepared in the form as per need in different form and determined by several related factors including the types of diseases to be treated, administration routes, patients age, gender, weight and severity of the illness [0108]. They teach that the pharmaceutical composition comprises pharmaceutically acceptable carriers such as a binder, a solubilizer, an excipient, a buffering agent, an isotonic agent [0109]. They teach that a formulation is in a form for solution (liquid), suspension or other forms and they comprise a carrier such as mannitol, sucrose, sorbitol, lactose [0110]. They teach that the pharmaceutical composition comprises stabilizer [0109].
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a liquid formulation having a glucagon derivative conjugated to an Fc via a non-peptide linker as taught A U 2013342321 in combination with Kim et al.1 which teaches a glucagon variant conjugated with an Fc in a formula X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071] and use the peptide X of amino acid sequence of SEQ ID NO: 37 as taught by 1-12 of U.S. Patent No. 10,696,725. Additionally, one would have been motivated to do so because Kim et al1. and AU 2013342321 teach glucagon derivatives conjugated with an Fc by a non-peptidyl linker. Further, one would have a reasonable expectation of success in using a glucagon derivative having amino acid sequence of SEQ ID NO: 37 as taught by claims 1-12 of US Pat. No. 10,686,725 in a liquid formulation as taught by AU 2013342321.
Claims 32-37 and 41-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,142,559 in view of AU 2013342321 (WO 2014/073842) and Kim et al.1 (US Pub. No.2017/013802). Claims 1-13 of US Pat. No. 11,142,559 teach a composition comprising a peptide moiety and biocompatible material moiety which is linked to the peptide moiety, wherein the peptide comprises the amino acid sequence of SEQ ID NO: 37 which is same as being instantly claimed (see PE2E search results). Claims 1-13 of US Pat. No. 11,142,559 also teach that the non-peptide linker is attached by thiol group of cysteine amino acid of the peptide. Claims 1-13 of US Pat. No. 11,142,559 teach that the biocompatible material is an Fc from IgG4. Claims 1-13 of US Pat. No. 11,142,559 do not teach a liquid composition comprising a buffering agent in amount of maintaining a pH of the liquid formulation in a range of 4.8 to 6.5 and 1% (w/v) to 20% (w/v) of sugar alcohol, a saccharide or a combination thereof.
AU 2013342321 teaches a liquid formulation of protein conjugate and an Fc, wherein the protein can be oxyntomodulin or glucagon for treating obesity (pg. 2, paragraph 6, pg. 5, paragraph [21])). They teach that the liquid formulation is albumin-free stabilizer, wherein the stabilizer contains a buffer, sugar alcohol, and non-ionic surfactant. They teach that the stabilizer may further include one or more components from isotonic agent, sugars, polyhydric alcohols and amino acids. They teach that the conjugate is in an effective amount (see pg. 6, para [26]) and it is noted that the effective amount of a peptide including GLP-1 variant, derivative or oxyntomodulin would be within the reach of one ordinary skill in the art. They teach using oxyntomodulin in a concentration of 10 mg/mL or 40 mg/mL, which would be within the range of 90 mmol/ml to 562 mmol/ml, unless evidence to contrary (see Tables 2, 26). They teach that sugar alcohol includes sorbitol, mannitol, glycerol in concentration of 2-15% (w/w) (page 6, para [24]). They teach that the buffer may include citrate, acetate, histidine or phosphate buffers to achieve a pH in the range of 4.5-7.0, more specifically 5-6 pH (pg.6, para [24], pg. 7, [29]). They teach that the isotonic agent may be NaCl, and non-ionic surfactant including polysorbate or poloxamer in a concentration of 0.0001-0.1% (w/v) (pg. 6 para [24]). They teach that the polysorbate is polysorbate 20 (pg. 6, para [26]). They teach that the amino acid may be methionine (page 6, para [24]).
Kim et al.1 teach a composition for prevention and treatment of diabetes including a long-acting insulinotropic peptide conjugate (see paragraph [0002]). They teach that the insulinotropic peptide includes GLP-1 and GLP-1 receptor agonists [0005]. They teach that a long-acting insulinotropic peptide is conjugated with an Fc via a non-peptidyl polymer as a linker by a covalent bond [0013]. They teach that the conjugate is represented by Formula: X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071]. They teach that the antibody fragment may be an Fc and can comprise a dimer or multimer formed from two or more fragments selected from the group consisting of IgG Fc, IgA Fc, IgM Fc, IgD Fc and IgE Fc fragments[0085]. They teach that the PEG is in a range of 1 to 20 kDa or 1 to 100kDa [0090].They teach that the pharmaceutical can be prepared in the form as per need in different form and determined by several related factors including the types of diseases to be treated, administration routes, patients age, gender, weight and severity of the illness [0108]. They teach that the pharmaceutical composition comprises pharmaceutically acceptable carriers such as a binder, a solubilizer, an excipient, a buffering agent, an isotonic agent [0109]. They teach that a formulation is in a form for solution (liquid), suspension or other forms and they comprise a carrier such as mannitol, sucrose, sorbitol, lactose [0110]. They teach that the pharmaceutical composition comprises stabilizer [0109].
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a liquid formulation having a glucagon derivative conjugated to an Fc via a non-peptide linker as taught A U 2013342321 in combination with Kim et al.1 which teaches a glucagon variant conjugated with an Fc in a formula X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071] and use the peptide X of amino acid sequence of SEQ ID NO: 37 as taught by 1-13 of U.S. Patent No. 11,142,559. Additionally, one would have been motivated to do so because Kim et al1. and AU 2013342321 teach glucagon derivatives conjugated with an Fc by a non-peptidyl linker. Further, one would have a reasonable expectation of success in using a glucagon derivative having amino acid sequence of SEQ ID NO: 37 as taught by claims 1-13 of US Pat. No. 11,142,559 in a liquid formulation as taught by AU 2013342321.
Claims 32-37 and 41-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-7 of U.S. Patent No. 11,667,688 in view of AU 2013342321 (WO 2014/073842) and Kim et al.1 (US Pub. No.2017/013802). Claims 1 and 3-7 of US Pat. No. 11,667,688 teach a composition comprising a peptide conjugate with a biocompatible material linked with a linker, wherein the peptide comprises amino acid sequence of SEQ ID NO: 37 which is identical to the instantly claimed peptide of SEQ ID NO: 37 and wherein the biocompatible material is an immunoglobulin Fc. Claims 1 and 3-7 of US Pat. No. 11,667,688 do not teach a liquid composition comprising a buffering agent in amount of maintaining a pH of the liquid formulation in a range of 4.8 to 6.5 and 1% (w/v) to 20% (w/v) of sugar alcohol, a saccharide or a combination thereof.
AU 2013342321 teaches a liquid formulation of protein conjugate and an Fc, wherein the protein can be oxyntomodulin or glucagon for treating obesity (pg. 2, paragraph 6, pg. 5, paragraph [21])). They teach that the liquid formulation is albumin-free stabilizer, wherein the stabilizer contains a buffer, sugar alcohol, and non-ionic surfactant. They teach that the stabilizer may further include one or more components from isotonic agent, sugars, polyhydric alcohols and amino acids. They teach that the conjugate is in an effective amount (see pg. 6, para [26]) and it is noted that the effective amount of a peptide including GLP-1 variant, derivative or oxyntomodulin would be within the reach of one ordinary skill in the art. They teach using oxyntomodulin in a concentration of 10 mg/mL or 40 mg/mL, which would be within the range of 90 mmol/ml to 562 mmol/ml, unless evidence to contrary (see Tables 2, 26). They teach that sugar alcohol includes sorbitol, mannitol, glycerol in concentration of 2-15% (w/w) (page 6, para [24]). They teach that the buffer may include citrate, acetate, histidine or phosphate buffers to achieve a pH in the range of 4.5-7.0, more specifically 5-6 pH (pg.6, para [24], pg. 7, [29]). They teach that the isotonic agent may be NaCl, and non-ionic surfactant including polysorbate or poloxamer in a concentration of 0.0001-0.1% (w/v) (pg. 6 para [24]). They teach that the polysorbate is polysorbate 20 (pg. 6, para [26]). They teach that the amino acid may be methionine (page 6, para [24]).
Kim et al.1 teach a composition for prevention and treatment of diabetes including a long-acting insulinotropic peptide conjugate (see paragraph [0002]). They teach that the insulinotropic peptide includes GLP-1 and GLP-1 receptor agonists [0005]. They teach that a long-acting insulinotropic peptide is conjugated with an Fc via a non-peptidyl polymer as a linker by a covalent bond [0013]. They teach that the conjugate is represented by Formula: X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071]. They teach that the antibody fragment may be an Fc and can comprise a dimer or multimer formed from two or more fragments selected from the group consisting of IgG Fc, IgA Fc, IgM Fc, IgD Fc and IgE Fc fragments[0085]. They teach that the PEG is in a range of 1 to 20 kDa or 1 to 100kDa [0090].They teach that the pharmaceutical can be prepared in the form as per need in different form and determined by several related factors including the types of diseases to be treated, administration routes, patients age, gender, weight and severity of the illness [0108]. They teach that the pharmaceutical composition comprises pharmaceutically acceptable carriers such as a binder, a solubilizer, an excipient, a buffering agent, an isotonic agent [0109]. They teach that a formulation is in a form for solution (liquid), suspension or other forms and they comprise a carrier such as mannitol, sucrose, sorbitol, lactose [0110]. They teach that the pharmaceutical composition comprises stabilizer [0109].
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a liquid formulation having a glucagon derivative conjugated to an Fc via a non-peptide linker as taught AU 2013342321 in combination with Kim et al.1 which teaches a glucagon variant conjugated with an Fc in a formula X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071] and use the peptide X of amino acid sequence of SEQ ID NO: 37 as taught by 1and 3-7 of U.S. Patent No. 11,667,688. Additionally, one would have been motivated to do so because Kim et al1. and AU 2013342321 teach glucagon derivatives conjugated with an Fc by a non-peptidyl linker. Further, one would have a reasonable expectation of success in using a glucagon derivative having amino acid sequence of SEQ ID NO: 37 as taught by claims 1 and 3-7 of US Pat. No. 11,667,688 in a liquid formulation as taught by AU 2013342321.
Claims 32-37 and 41- 56 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 7, 10, 16 and 17 of copending Application No. 17/766,137 in view of AU 2013342321 (WO 2014/073842) and Kim et al.1 (US Pub. No.2017/013802). Claims 1-2, 5,7,10,16 and 17 teach a conjugate comprising a peptide of amino acid sequence of SEQ ID NO: 37 wherein the conjugate is represented by the formula 1: X-L-F, wherein the X is a peptide, L is linker and F is immunoglobulin Fc region, wherein a C-terminal of the peptide is amidated, wherein ethylene glycol repeating unit L has molecular weight in a range of 1 kDa to 100 kDa. Claims 1-2, 5, 7, 10, 16 and 17 of copending Application No. 17/766,137 do not teach a liquid composition comprising a buffering agent in amount of maintaining a pH of the liquid formulation in a range of 4.8 to 6.5 and 1% (w/v) to 20% (w/v) of sugar alcohol, a saccharide or a combination thereof.
AU 2013342321 teaches a liquid formulation of protein conjugate and an Fc, wherein the protein can be oxyntomodulin or glucagon for treating obesity (pg. 2, paragraph 6, pg. 5, paragraph [21])). They teach that the liquid formulation is albumin-free stabilizer, wherein the stabilizer contains a buffer, sugar alcohol, and non-ionic surfactant. They teach that the stabilizer may further include one or more components from isotonic agent, sugars, polyhydric alcohols and amino acids. They teach that the conjugate is in an effective amount (see pg. 6, para [26]) and it is noted that the effective amount of a peptide including GLP-1 variant, derivative or oxyntomodulin would be within the reach of one ordinary skill in the art. They teach using oxyntomodulin in a concentration of 10 mg/mL or 40 mg/mL, which would be within the range of 90 mmol/ml to 562 mmol/ml, unless evidence to contrary (see Tables 2, 26). They teach that sugar alcohol includes sorbitol, mannitol, glycerol in concentration of 2-15% (w/w) (page 6, para [24]). They teach that the buffer may include citrate, acetate, histidine or phosphate buffers to achieve a pH in the range of 4.5-7.0, more specifically 5-6 pH (pg.6, para [24], pg. 7, [29]). They teach that the isotonic agent may be NaCl, and non-ionic surfactant including polysorbate or poloxamer in a concentration of 0.0001-0.1% (w/v) (pg. 6 para [24]). They teach that the polysorbate is polysorbate 20 (pg. 6, para [26]). They teach that the amino acid may be methionine (page 6, para [24]).
Kim et al.1 teach a composition for prevention and treatment of diabetes including a long-acting insulinotropic peptide conjugate (see paragraph [0002]). They teach that the insulinotropic peptide includes GLP-1 and GLP-1 receptor agonists [0005]. They teach that a long-acting insulinotropic peptide is conjugated with an Fc via a non-peptidyl polymer as a linker by a covalent bond [0013]. They teach that the conjugate is represented by Formula: X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071]. They teach that the antibody fragment may be an Fc and can comprise a dimer or multimer formed from two or more fragments selected from the group consisting of IgG Fc, IgA Fc, IgM Fc, IgD Fc and IgE Fc fragments[0085]. They teach that the PEG is in a range of 1 to 20 kDa or 1 to 100kDa [0090].They teach that the pharmaceutical can be prepared in the form as per need in different form and determined by several related factors including the types of diseases to be treated, administration routes, patients age, gender, weight and severity of the illness [0108]. They teach that the pharmaceutical composition comprises pharmaceutically acceptable carriers such as a binder, a solubilizer, an excipient, a buffering agent, an isotonic agent [0109]. They teach that a formulation is in a form for solution (liquid), suspension or other forms and they comprise a carrier such as mannitol, sucrose, sorbitol, lactose [0110]. They teach that the pharmaceutical composition comprises stabilizer [0109].
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a liquid formulation having a glucagon derivative conjugated to an Fc via a non-peptide linker as taught AU 2013342321 in combination with Kim et al.1 which teaches a glucagon variant conjugated with an Fc in a formula X-La-F (see [0070]), wherein X ins an insulinotropic peptide, L is a linker, a is 0 or a natural number (when a is 2 or higher each L is independent), F is an antibody fragment or FcRn binding material [0071] and use the peptide X of amino acid sequence of SEQ ID NO: 37 as taught by claims 1-2, 5, 7, 10, 16 and 17 of copending Application No. 17/766,137. Additionally, one would have been motivated to do so because Kim et al1. and AU 2013342321 teach glucagon derivatives conjugated with an Fc by a non-peptidyl linker. Further, one would have a reasonable expectation of success in using a glucagon derivative having amino acid sequence of SEQ ID NO: 37 as taught by claims 1-2, 5, 7, 10, 16 and 17 of copending Application No. 17/766,137 in a liquid formulation as taught by AU 2013342321.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674